Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma.

Pei-Yi Chu,Kuo-Wang Tsai,Shih-Hsuan Chan,Fang-Ping Shen,Shiao-Lin Tung

doi:10.3390/cancers12071843

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, affecting over 700,000 people per year. The treatment effect in advanced HCC is still disappointing and prognosis of advanced HCC remains poor. Hence, to find more effective therapeutic targets to improve the treatment outcome of HCC is of urgent need. In this study, we reported the novel oncogenic function of SAAL1 (serum amyloid A-like 1) in HCC, which previously is considered as an inflammation-related gene. We found that SAAL1 was significantly upregulated in HCC tumor tissues when compared to the adjacent normal tissues and high expression of SAAL1 correlated with shorter overall survival in The Cancer Genome Atlas (TCGA) HCC database. Functionally, we showed that the depletion of SAAL1 significantly reduced cell proliferation, 3D colony formation, and migration/invasion abilities of HCC cancer cells. Furthermore, suppression of SAAL1 impaired the HGF/Met-driven Akt/mTOR phosphorylation cascade and increased the chemosensitivity of HCC cells to sorafenib and foretinib treatment. Our data indicated that SAAL1 plays an important role in HCC via mediating oncogenic HGF/Met-driven Akt/mTOR signaling and could serve as an independent prognostic marker, as well as a promising therapeutic target for HCC patients.

Highlights

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, affecting over 700,000 people per year [1,2]
We demonstrated that depletion of Serum amyloid A-like 1 (SAAL1) in HCC cells led to the inhibition of cell proliferation and anchorage-independent growth, as well as migration/invasion abilities via impairing Hepatocyte growth factor (HGF)/Met-driven Akt/mTOR oncogenic signaling
Univariate Cox’s regression analysis showed that high levels of SAAL1 resulted in poor overall survival of HCC patients (crude hazard ratio [CHR], 1.63; 95% confidence interval (CI), 1.13–2.35; p = 0.009)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, affecting over 700,000 people per year [1,2]. Curative surgical resection or liver transplantation or local therapy, such as transarterial chemoembolization (TACE) failed to show significant efficacy in prolonging overall survival in advanced HCC, the treatment effect of conventional chemotherapeutic agents such as doxorubicin in advanced HCC is disappointing [8]. In spite of new targeted therapies and immunotherapeutic agents such as sorafenib, regorafenib, cabozantinib, lenvatinib, and nivolumab were applied to treat advanced HCC, the prognosis of advanced HCC remains poor with a median survival of less than two years [9,10,11,12,13]. Based on the above-mentioned facts, HCC is still one of the hard-to-treat human malignancies, and more effective therapeutic approaches to improve the treatment outcome of HCC are in an urgent need

Methods

Results

Conclusion